Sialic acid is a naturally occurring component of human breast milk, where it is found associated with various oligosaccharides and glycoproteins. While human breast milk contains substantial amounts of sialic acid, most infant formulas contain less than 25% of the sialic acid found in colostrum. Moreover, 70% of the sialic acid in formulas is glycoprotein-bound, unlike human breast milk in which 75% of sialic acid is bound to oligosaccharides. See Heine, W., et al., Monatsschr Kinderheilkd 141:946-50 (1993), Wang, B., et al., Am J Clin Nutr 74:510-5 (2001), and Nakano, T., et al, Acta Paediatr Taiwan 42:11-17 (2001). Not surprisingly, the accumulation of sialic acid by breast-fed infants is generally higher than for formula-fed infants. See Wang, B., et al., J Pediatr 138:914-6 (2001). Evidence suggests that N-acetyineuraminic acid (NANA, or sialic acid) is important in the development and function of the neonatal brain where it is a major component of gangliosides. See Carlson, S. E., Am J Clin Nutr 41:720-6 (1985), Morgan, B. and Winnick, M., J Nutr 110:416-24 (1980), Svennerholm, L., et al., Biochim Biophys Acta 1005:109-17 (1989), and Wang, B., et al., Comp Biochem Physiol A Mol Integr Physiol 435-9 (1998). Therefore, infants fed commercial formulas may not be acquiring sufficient quantities of a nutrient important for early development.
Cow's milk-based formulas generally have low sialic acid content. In one study, the concentration of sialic acid in several casein/whey combination formulas was less than 200 mg sialic acid/L. Moreover, soy protein-based formulas contain substantially reduced levels of sialic acid as compared to cow's milk-based formula. Therefore, formulas that are both lactose free and soy protein-based would exhibit very low sialic acid content.
There are several known sources of sialic acid in its various conjugated forms. These include, but are not limited to, free N-acetylneuraminic acid (or sialic acid), the oligosaccharide sialyllactose, sialic acid-containing gangliosides, and the protein casein macropeptide (CMP), also referred to as glycomacropeptide (GMP).
The addition of sialic acid or sources of sialic acid to certain nutritional formulas is somewhat known in the art. For example, U.S. Pat. No. 6,506,422 discloses a particular nutritional formula containing casein glycomacropeptide and complimentary essential amino acids other than phenylalanine for administration to patients suffering from phenylketonuria. The levels of sialic acid found in infant formulas are not mentioned.
U.S. Pat. No. 6,270,827, discloses a formulation containing human milk proteins or recombinant host resistance factors, one of which is recombinant human kappa-casein, to supplement synthetic infant formulas.
U.S. Pat. No. 4,762,822 discloses the use of N-acetylneuraminic acid or gangliosides containing sialic acid in infant formula to protect the newborn from gastrointestinal disease-producing organisms.
International patent application WO 01/60346 A2 discloses a nutritional formulation containing the oligosaccharides oligofructose and sialyllactose as prebiotic substances to promote the growth of bifidobacteria in the gut that may be used in conjunction with infant formula.
While the use of sialic acid and sialic acid sources in infant formula appears to be present in some of the prior art, the particular features of the present invention which provide a nutritionally complete infant formula with enhanced amounts of sialic acid similar to breast milk are absent therefrom.